PATHOLOGY

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PATHOLOGY
"Where there is love of medicine, there is love
of humankind"
Hippocrates
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Pathology Dept

• Doç. Dr. Isin Dogan Ekici
• Prof. Dr. Ferda Özkan

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(pathos) (logos)

• Pathology literally is the study (logos) of
  suffering (pathos).
• More specifically, it is a bridging discipline
  involving both
• basic science and
• clinical practice and is devoted to the study of
  the structural and functional changes in cells,
  tissues, and organs that underlie diseases.

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• By the use of molecular, microbiologic,
  immunologic, and morphologic techniques,
  pathology attempts to explain the whys of the
  signs and symptoms manifested by patients while
  providing a sound foundation for rational
  clinical care and therapy.

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Cell Injury Functional Derangement and Symptoms

• Cellular dysfunction ? Organ dysfunction ?
  Clinical disease
• This concept dates to the 19th century and
  Rudolph Virchow, the father of modern pathology
• pathology is the study of cell injury and the
  expression of pre-existing capacity to adapt to
  such injury

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• Traditionally, the study of pathology is divided
  into
• general pathology,
• special or systemic pathology.
• The former is concerned with the basic reactions
  of cells and tissues to abnormal stimuli that
  underlie all diseases.
• The latter examines the specific responses of
  specialized organs and tissues to more or less
  well-defined stimuli.

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• Histopathology
• Cytopathology
• Hematology
• Microbiology
• Immunology
• Chemical Pathology
• Genetics
• Toxicology
• Forensic Pathology

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• For understanding pathology It requires
  correlation between normal Anatomy, Histology and
  Physiology and the process resulting in the
  manifestations of disease.

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• The four aspects of a disease process that form
  the core of pathology are
• (1)   its cause (etiology),
• (2)   the mechanisms of its development
  (pathogenesis),
• (3)   the structural alterations induced in the
  cells and organs of the body (morphologic
  changes), and
• (4) the functional consequences of the
  morphologic changes (clinical significance).

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1. Etiology or cause

• The concept that certain abnormal symptoms or
  diseases are caused is as ancient as recorded
  history.
• For the Acadians (2500 B.C.), if someone became
  ill, it was
• the patients own fault (for having sinned) or
• the makings of outside agents, such as bad
  smells, cold, evil spirits, or gods.

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• In modern terms, there are the two major classes
  of etiologic factors
• intrinsic or genetic,
• acquired (e.g., infectious, nutritional,
  chemical, physical).
• Knowledge or discovery of the primary cause
  remains the backbone on which a diagnosis can be
  made, a disease understood, or a treatment
  developed.

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• The concept, however, of one etiologic agent to
  one diseasedeveloped from the study of
  infections or single gene disordersis no longer
  sufficient.
• Genetic factors affect acquired diseases,
• Environment has profound effect on genetic
  diseases.

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Classification of Diseases

• Developmental
• Inflammatory
• Neoplastic
• Degenerative

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Disease etiology (vindicatesss)

• Vascular (atherosclerosis, thrombosis)
• Infectious (viral, bacterial, mycobacterial,
  spirochetal, fungal, protozoal, and arthropod)
• Neoplastic (both benign and malignant tumors)
• Drugs or toxins
• Inflammatory/idiopathic
• Congenital (chromosomal abnormalities, gene
  defects)
• Autoimmune disorders (lupus, rheumatoid
  arthritis)
• Trauma or environmental (heat, cold, vitamin
  deficiencies, nutritional)
• Endocrine/Metabolic (diabetes, acidosis)
• Supernatural, Supra-tentorial, or Something else.

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• The sequence of events in response to cell
  injury, from whatever etiology, that leads to the
  ultimate expression of the disease (symptoms)
• Many times the pathogenesis or etiology is
  unknown, in which case we say that the disease
  pathogenesis is idiopathic.

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2. Pathogenesis

• Pathogenesis refers to the sequence of events in
  the response of the cells or tissues to the
  etiologic agent, from the initial stimulus to the
  ultimate expression of the disease.
• Gross and Microscopic Structure, Function,
  Chemistry Molecular mechanisms.
• The study of pathogenesis remains one of the main
  domains of pathology.

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3. Morphologic changes

• The morphologic changes refer to the structural
  alterations in cells or tissues that are either
  characteristic of the disease or diagnostic of
  the etiologic process.

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• Gross Pathology
• Light Microscopy
• Histochemistry
• Immunohistochemistry
• Electron Microscopy
• Cell Cultures, Medical Microbiology
• Molecular Pathology

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4. Functional derangements and clinical
significance

• The nature of the morphologic changes and their
  distribution in different organs or tissues
  influence normal function and determine the
  clinical features (symptoms and signs), course,
  and prognosis of the disease.

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Definitions

• The normal cell is confined to a fairly narrow
  range of function and structure by its
• genetic programs of metabolism,
• differentiation,
• specialization.
• More excessive physiologic stresses or some
  pathologic stimuli ? a number of physiologic and
  morphologic cellular adaptations.

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• If the limits of adaptive response to a stimulus
  are exceeded, or in certain instances when
  adaptation is not possible, a sequence of events
  follows, loosely termed cell injury.
• Cell injury is reversible up to a certain point,
  but if the stimulus persists or is severe enough
  from the beginning, the cell reaches the point of
  no return and suffers irreversible cell injury
  and cell death.

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Terminology
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• Disease things which interfere with a person's
  ability to work, to play, and/or happiness.
• There really are a lot of distinct diseases, and
  when you understand how they arise, it's easy to
  figure out how to treat them.
• Symptom What the patient tells to the doctor.
• Sign/finding What the doctor finds to help with
  the diagnosis.
• Morphology altered shapes in disease.
• Pathognomonic Occurs only in one disease,
  enabling you to make the diagnosis.
• Pathogen Generally it is a microorganism that
  causes disease.

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• Organic disease The pathologist can exhibit a
  clear lesion.
• Functional disease The pathologist cannot
  exhibit a clear lesion (migraine,
  fibromyalgia,...).
• Psychosomatic disease Anything about the
  mind-body interface.
• Paleopathology is the study of disease as shown
  in human remains from primitive societies.

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• Lesions are fundamental pathologic changes
  (usually anatomic derangements, though they may
  be molecular) that the pathologist can exhibit.
• A syndrome is a cluster of related symptoms
  and/or signs not necessarily due to the same
  causes in different patients, but typically due
  to a single cause in any individual patient.
• The diagnosis is the name given to the particular
  disease, once it is identified.
• The prognosis of a disease is the expected
  outcome for a particular case.

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• Tissue Handling and Processing

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Preparetion of the tissues for routine pathologic
examination.

• Formaline, formaldehyde (10) major fixative
  solution
• All of the tissues must send to the pathology
  laboratory following the steps below
• Put the tissue in a plastic jar,
• Add formaline solution,
• Close the lid of the jar,
• Print the patients name and paste the barcode on
  the jar.
• Do not forget to write your name and the
  patients name, age, clinical findings,
  preliminary diagnosis and operation notes in the
  pathology form.
• Send them immediately to the pathology lab.

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Exceptions

• If you are sending the tissue for frozen section
  or
• If you are sending the tissue for
  immunoflouresceint or flow cytometry
• Put the tissue in a saline embedded wet towel
  instead of formaline!!!
• If you forget those details do not hesitate to
  phone and ask to the pathologyst!!!

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MacroscopyGross examination
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Autopsy
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Dissection
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Cassettes
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Tissue processing

• Preparation of the tissues for routine histologic
  examination.
• Simply
• Dehydration of tissues by using alcohol,
  claryfying the tissue by using xylol and infusing
  paraffin.

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Tissue processors
Dehydration of tissues by using alcohol,
claryfying the tissue by using xylol and finally
infusing paraffin.
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Embedding sectioning

• Microtome

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• Staining

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FrozenCryostate
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Cytology

• Body fluids
• Exfoliative cytology (smears)
• Aspiration biopsies

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Cytology
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Microscopic examination
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SPECIAL STAINS
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• Hematoxylin and eosin (HE)
• The standard tissue stain.
• Hematoxylin stains nucleic acids, calcium salts,
  and bacteria blue-purple.
• Eosin (red) binds to free amino groups and thus
  stains arginine and lysine (cytoplasm, hyaline,
  amyloid, osteoid, ect) pink.

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• Periodic acid-Schiff (PAS)
• Periodic acid (HIO4-) oxidation (cis-diols to
  aldehydes) and Schiff-base reactions.
• Anything with a cis-dihydroxy group, i.e.,
  insoluble sugar compounds such as
• glycogen
• epithelial mucin
• cartilage
• fungus wall
• basement membranes
• reticulin
• alpha-1 protease inhibitor (antitrypsin)
• type I collagen (weak)
• all amyloids (weak)
• gets stained magenta.

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• Diastase-PAS ("d-PAS") is the PAS reaction
  performed on tissue previously digested by
  diastase, which removes glycogen.
• Reticulin stains the delicate fibers that
  surround small blood vessels and hold together
  liver, spleen, and lymph nodes.
• Prussian Blue uses a special solution of
  ferrocyanide. By the familiar reaction, it stains
  all exposed ferric ions very blue.
• Sudan / Oil Red O are oil-based stains that can
  only be used on thin slices ("frozen sections")
  of tissue from which fat has not been removed.
• These stain only fat (usually black or bright
  red).
• Mucicarmine is a special dye that stains only
  epithelial mucin (usually red). The actual
  chemistry remains mysterious.

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• Congo Red is a special dye that fits tightly into
  beta-pleated proteins of all sorts.
• Beta-pleated proteins in humans are abnormal and
  are called amyloids.
• Congo Red stains all amyloids brick red, and
  everything else pink.
• Because of the way beta-pleated sheets line up
  Congo Red, amyloids also acquire an apple green
  birefringence when stained with Congo Red and
  then examined under polarized light.
• Alcian blue stains certain mucoid substances
  (hyaluronic acid, sulfomucin, maybe carboxymucin
  depending on the recipe).
• Trichrome uses familiar aniline dyes to stain
  collagen (type I, also basement membranes) blue
  or green and everything else some other color.

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• Acid-fast stains (ZN, auramine O, others) stain
  certain waxes a permanent red (or some other
  color).
• This shows up mycobacteria (TB bugs) and certain
  other rare substances.
• Argentaffin stains test the ability of cell
  structures to bind and reduce silver, while
  argyrophil stains demonstrate all sites of silver
  binding, whether or not reduction occurs.
• Methenamine silver is a great stain for fungi and
  pneumocystis. It stains them black.
• Elastic stains (Verhoeff, Van Gieson) selectively
  stain elastic fibers.

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• Metachromatic stains A single dye will impart a
  variety of hues to different structures.
• The most important metachromatic dyes are those
  use to stain blood and bone marrow smears (the
  various azures)
• Bismark brown imparts a metachromatic yellow on
  pap smears.
• Papanicolaou's stain is used for cytology (i.e.,
  smears of cells on glass slides, "Pap" smears).
• Methyl green pyronine stains RNA red and
  everything else green.

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• Immunostaining (immunofluorescence,
  immunoperoxidase) uses monoclonal antibodies to
  demonstrate specific antigens (i.e., specific
  proteins) in tissues.
• Nucleic acid probes are now being introduced to
  stain particular genes and their RNA's.
• For example, a cancer cell which contains mRNA
  for albumin must be of hepatocyte origin.

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